12-methoxydodecanoic acid (12-MO) is a heteroatom fatty acid analog of myristic acid that exhibits potent anti-HIV activity and 12MO is therefore a biologically active fatty acid. Diacylated phosphatidylcholine containing 12MO in both the sn-1 and sn-2 position of the glycerobackbone was synthesized (and this anti-HIV compound is denoted as AC2) is more potent and less toxic than 12MO. In three different anti-HIV assays (i.e., syncytial assays, reverse transcriptase assays, T-Cell cytopathic assays), AC2 exhibits approximately 4 fold increased activity compared to the free fatty acid 12MO. AC2 contains 2 equivalents of AC2 and this 4 fold increased activity exceeds the expected 2 fold increase activity if the cellular availability and cellular disposition of free 12MO is identical to 12MO tethered to the phospholipid molecule. In addition, we have demonstrated potent synergism with AC2 and AZT in T-cells. The primary objective of this work is to perform a comprehensive structure activity relationship (SAR) of single chain and double chain phospholipids, which contain biologically active compounds as alkyl chains, regarding anti-HIV activity in both T-cells and macrophages. Thus single and double chain phospholipid analogs containing 12MO will be prepared with different lipid headgroups: phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidic acid (PA). The metabolic rate of diacylated and monoacylated phospholipids bearing biologically active fatty acids will be determined in human T-cells and macrophages. this metabolite information is critical for designing heteroatom-fatty- acids and phospholipids as drugs for AIDS.